The discipline of Clinical Pharmacology seeks to apply an understanding of the fundamental mechanisms of drug action to improve the therapy of human diseases. The Division of Clinical Pharmacology at Vanderbilt offers an outstanding research-based fellowship program committed to training future leaders in the discipline. The 19 faculty members in the Division, along with 29 selected faculty members in other departments, constitute the mentoring faculty for this postdoctoral training program. Collaborations among investigators focusing on common research themes are well established in the Division;these research areas include (1) drug disposition and metabolism, (2) eicosanoid and lipid mediator biology and pharmacology, (3) vascular pharmacology and control of the circulation, and (4) ion channel pharmacology and arrhythmia pharmacogenomics. Additional collaborative efforts exist in cancerpharmacology, neuropharmacology and pharmacoepidemiology, among others. The primary activity of trainees is research training in a mentored setting on issues directly relevant to mechanisms of drug action. Research can vary from bench-based to clinical studies. There are currently 22 fellows in the program and six are supported by this grant. The duration of training is two to three years and individuals holding either an M.D., Ph.D. or Pharm.D. are supported. Research training under the direction of individual faculty mentors is supplemented by didactic course work and seminars. Required courses of trainees include research ethics, biostatistics and study design, drug regulation and development, and pharmacokinetics/ pharmacodynamics. In addition, attendance at Clinical Pharmacology Grand Rounds and a new established Fellows'Lecture Series is required. This curriculum supplements the trainees'research experience and provides a knowledge base that will allow for fellows to develop into successful leaders in clinical pharmacology. Trainees also participate in the clinical services of the Division including Hypertension, Medical Toxicology, Arrhythmia, and Autonomic Dysfunction. Recent commitments by Vanderbilt to grow Clinical Pharmacology offer a unique opportunity to further enhance the training program. These include the opening of the Oates Institute of Experimental Therapeutics, recruitment of new faculty, and the establishment of new programs in drug discovery. The overall mission of the Vanderbilt Clinical Pharmacology training program is to train investigators who will ultimately assume leadership positions in the discipline. Of trainees supported by the award since its inception in 1977, approximately 80% are in academic medicine, industry or government. Clinical Pharmacology at Vanderbilt is a vibrant and dynamic enterprise poised for significant growth. As a consequence, support for ten training positions per year is requested in this renewal.